Long-term Follow-up of Laparoscope-Assisted Living Donor Hepatectomy.

BACKGROUND: We have introduced and performed laparoscope-assisted surgery in living donor hepatectomy. The objective of this study was to investigate the long-term results of laparoscope-assisted living donor hepatectomy. METHODS: From 2006 to 2016, laparoscope-assisted living donor hepatectomy was performed in 11 patients (laparoscopic group), and conventional open living donor hepatectomy was performed in 40 patients (conventional group). Intraoperative and postoperative complications were evaluated according to the Clavien-Dindo classification and analyzed in the laparoscopic group for comparison with the conventional group. RESULTS: The median postoperative follow-up period was 88 months (range, 58-120 months) in the laparoscopic group. One donor in the conventional group died from a motor vehicle crash 16 months after surgery. All others were alive and returned to their preoperative activity level. Regarding intraoperative and early (≤90 days after surgery) postoperative complications, 1 patient (1/11, 9%) showed biliary fistula (Grade IIIa) in the laparoscopic group. In the conventional group, 6 patients (6/40, 15%) showed surgical complications of Grade I in 2 patients and Grade II in 4 patients. Regarding late (>90 days after surgery) postoperative complications, biliary stricture was observed in 1 patient of the laparoscopic group; this patient developed hepatolithiasis 6 years after surgery, and endoscopic lithotomy and extracorporeal shockwave lithotripsy were performed, resulting in successful treatment. Late complications were not observed in the conventional group. CONCLUSION: One donor in the laparoscopic group showed Grade IIIa late complications. The introduction of laparoscopic surgery to living donor hepatectomy should be performed carefully.

Study of Immune Tolerance Cases in Adult Living Donor Liver Transplantation.

BACKGROUND: Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS: A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS: Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipient's child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS: In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.

Successful Endoscopic Management of Acute Necrotic Pancreatitis and Walled Off Necrosis After Auxiliary Partial Orthotopic Living-Donor Liver Transplantation: A Case Report.

Endoscopic management of acute necrotic pancreatitis and walled off necrosis is less invasive than surgical treatment and has become the 1st choice for treating pancreatic necrosis and abscess. We treated a case of acute necrotic pancreatitis and walled off necrosis after auxiliary partial orthotopic living-donor liver transplantation (APOLT). A 24-year-old woman was admitted to our university hospital for removal of the internal biliary stent, which had already been placed endoscopically for the treatment of biliary stricture after APOLT. She had been treated for acute liver failure by APOLT 10 years before. After we removed the internal stent with the use of an endoscopic retrograde approach, she presented with severe abdominal pain and a high fever. Her diagnosis was severe acute pancreatitis after endoscopic retrograde cholangiography (ERC). Her symptoms worsened, and she had multiple organ failure. She was transferred to the intensive care unit (ICU). Immunosuppression was discontinued because infection treatment was necessary and the native liver had already recovered sufficiently. After she had been treated for 19 days in the ICU, she recovered from her multiple organ failure. However, abdominal computerized tomography demonstrated the formation of pancreatic walled off necrosis and an abscess on the 20th day after ERC. We performed endoscopic ultrasonography-guided abscess drainage and repeated endoscopic necrosectomy. The walled off necrosis diminished gradually in size, and the symptoms disappeared. The patient was discharged on the 87th day after ERC. This is the 1st report of a case of acute necrotic pancreatitis and walled off necrosis that was successfully treated by endoscopic management after APOLT.

Successful Re-resection for Locally Recurrent Retroperitoneal Liposarcoma at Four Years After Ex Vivo Tumor Resection and Autotransplantation of the Liver: A Case Report.

Surgical resection should be considered for isolated locally recurrent retroperitoneal liposarcomas. We experienced a case of successful re-resection for locally recurrent retroperitoneal liposarcomas 4 years after ex vivo tumor resection and autotransplantation of the liver. A 75-year-old man was admitted to our hospital. His diagnosis was local recurrence of liposarcomas. He had previously undergone ex vivo tumor resection and autologous orthotopic liver transplantation for a retroperitoneal tumor 4 years earlier. The resected tumor size was 23.5 × 15.5 × 12.5 cm. The tumor was revealed by means of histopathologic study to be a myxoid liposarcoma. Follow-up computerized tomography showed 2 recurrent tumors in the retropancreatic and para-aortic lesions. Although adhesion was severe within the operative field, we successfully performed complete en bloc re-resection of each recurrent tumor. The operative time was 250 minutes, and blood loss was 300 mL. The resected tumor sizes were 3.9 × 3.2 × 1.5 cm and 4.5 × 3.3 × 3.0 cm. The tumors were revealed by means of histopathologic study to be dedifferentiated liposarcomas. Postoperative complications included intestinal obstruction and colocutaneous fistula formation, both of which were treated surgically. The patient was discharged in an ambulatory state at 80 days after re-resection of the recurrent tumors. At the time of writing, he was alive with no evidence of recurrence, 14 months after re-resection and 62 months after primary ex vivo tumor resection. This is the first case of successful surgical re-resection for locally recurrent liposarcoma after ex vivo tumor resection and autotransplantation of the liver.

Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report.

BACKGROUND: Long-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified. METHODS: We have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function. RESULTS: The patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 µg/d. CONCLUSIONS: Our patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.

Structured Ni catalysts on porous anodic alumina membranes for methane dry reforming: NiAl2O4 formation and characterization.

This communication presents the successful design of a structured catalyst based on porous anodic alumina membranes for methane dry reforming. The catalyst with a strong Ni-NiAl2O4 interaction shows both excellent activity and stability.

Switching to an L/N-type calcium channel blocker shows renoprotective effects in patients with chronic kidney disease: the Kyoto Cilnidipine Study.

OBJECTIVE: This open-label, randomized controlled trial investigated the effects of cilnidipine, an L/N-type calcium channel blocker (CCB), in patients with chronic kidney disease (CKD). METHODS: Sixty patients with CKD and well-controlled hypertension being treated with a renin- angiotensin system (RAS) inhibitor and an L-type CCB (L-CCB) were randomly assigned either to switch from the L-CCB to cilnidipine after a 4-week observation period or to continue with L-CCB treatment. Blood pressure, heart rate and renal function were monitored for 12 months. Data were available for analysis from 50 patients: 24 from the cilnidipine group and 26 from the L-CCB group. RESULTS: Blood pressure was well controlled in both groups. After 12 months, proteinuria and heart rate were significantly decreased in the cilnidipine group, but proteinuria increased and heart rate remained unchanged in the L-CCB group. There was a significant positive correlation between the percentage changes in proteinuria and heart rate. CONCLUSIONS: Cilnidipine has antihypertensive effects equivalent to those of L-CCBs. In patients with CKD, proteinuria can be decreased by switching from an L-CCB to cilnidipine, thereby improving renal function.

Histamine ameliorates anti-glomerular basement membrane antibody-induced glomerulonephritis in rats.

Anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis involves T-helper type 1 (Th1) responses leading to rapid crescent formation. As many inflammatory and immune responses in general are affected by histamine, we examined the effects of histaminergic ligands on immune renal injury in the rat. Female Wistar-Kyoto rats were injected intraperitoneally with an antibody against the GBMs. Histaminergic ligands were then injected twice daily for 5 days after which renal function was assessed by proteinuria. Treatment with histamine led to significant dose-dependent reductions in proteinuria compared to the control antibody-injected group and markedly decreased the number of crescentic glomeruli and macrophage infiltration of the glomeruli. Furthermore, histamine significantly decreased the plasma concentration of interleukin-12, a Th1-type cytokine compared to the antibody-injected control animals. Dimaprit, an H(2)/H(4) agonist, mimicked the effects of histamine on proteinuria and crescent formation. Clozapine, an H(4) agonist, tended to mimic the effects of histamine, whereas an H(1), mepyramine, or an H(2) antagonist, ranitidine, did not reverse the protective effect of histamine. We suggest that histamine may alleviate renal injury in anti-GBM glomerulonephritis by suppressing the immune response.

Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic arteriopathy presenting with migraines, mood disorders, focal neurologic deficits, recurrent ischemic attacks and dementia in young adults. The genesis of this disease relates to missense mutation of the Notch3 gene. We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extraglomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss of vascular smooth muscle cells and subsequent intimal thickening. Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney.

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

Changes in serum LECT 2 levels during the early period of liver regeneration after adult living related donor liver transplantation.

We investigated changes in serum leukocyte cell-derived chemotaxin2 (LECT2) levels between donors and recipients in the early period during liver regeneration following adult living related donor liver transplantation (LRDLT). Five recipients (three women, two men; 37.0 +/- 15.8 years old), all of whom had end-stage liver failure, underwent LRDLT from healthy five donors (two women, three men; 41.6 +/- 14.3 years old) between June 2000 and February 2001. FK506 and methylprednisolone were used as immunosuppressants for recipients. Serum LECT2 levels decreased immediately after both the hepatectomy in all donors and the implantation of liver graft in all recipients. Donors showed a nadir at 3 to 12 hours, increasing at 24 to 48 hours. The nadir in recipients occurred several hours after the donors. The serum LECT2 levels of donors were significantly higher than those of recipients on day 5 (9.5 +/- 5.9 ng/mL vs 3.1 +/- 2.2 ng/mL, P = .04) and on day 7 (9.3 +/- 3.8 ng/mL vs 3.5 +/- 1.1 ng/mL, P = .04). Serum GPT and GOT levels were inversely proportionate to the serum LECT2 levels. The present studies suggest that LECT2 participates in liver regeneration and injury following hepatectomy.

Serum LECT2 level as a prognostic indicator in acute liver failure.

In the present study, we investigated the relationship between serum leukocyte cell-derived chemotaxin2 (LECT2) levels and liver function in patients with acute liver failure, and its use as a prognostic indicator. We studied six acute liver failure patients (two women, four men; 49.8 +/- 20.7 years old) admitted to our hospital in 2002. These patients had diagnoses of fulminant hepatitis due to acute liver failure (1) from congestive heart failure; (2) from portal venous gas, and (3) from postoperative disseminated intravascular coagulation (DIC). We measured serum LECT2, GOT, and GPT levels, the last two being inversely proportionate to the serum LECT2 levels. When the serum GPT levels peaked, the serum LECT2 levels were the lowest. When the liver function recovered, serum LECT2 levels increased. Three of four patients died due to liver failure, one to congestive heart failure. Maximum serum LECT2 levels among the expired group were significantly lower than those among the alive group (0.96 +/- 0.8 ng/mL vs 12.9 +/- 4.3 ng/mL). Serum LECT2 levels may be a prognostic indicator of recovery from liver failure. The present study suggests that in clinical medicine LECT2 participates in regeneration after injury of hepatocytes.

Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue.

Denatured syngeneic liver tissue prepared by mechanical procedures was intraperitoneally injected into adult C57BL/6 mice. In parallel with a decrease in the total number of lymphocytes in the liver, spleen, and thymus from days 1-7 after the injection, the proportion of the CD4+NK1.1+CD3(int) subset of these cells (i.e. natural killer T or NKT cells) increased in the liver. Even the absolute number of these NKT cells increased in the liver on days 14 and 21. In response to the injection of denatured liver tissue, tissue damage was induced in the liver, as shown by elevated levels of serum transaminases and hepatocyte degeneration observed by electron microscopy. Sera obtained on days 7 and 14 contained autoantibodies including anti-DNA antibodies. The proportion of CD1d(high)B cells in the liver was found to decrease on days 1-7. In other words, denatured liver tissue stimulated both NKT cells and certain B cells in the liver. These results suggest that liver lymphocytes might contain not only autoreactive T cells (e.g. CD3(int) or NKT cells) but also some B cells (e.g. B-1 cells) which produce autoantibodies and that the denatured tissue had the potential to stimulate these lymphocytes and to evoke an autoimmune-like state.

Abundance of unconventional CD8(+) natural killer T cells in the large intestine.

Natural killer T (NKT) cells are mainly present in the liver and thymus, and the majority of these T cells express either a CD4(+) or a double-negative (DN) CD4(-)8(-) phenotype. In the present study, we examined whether such NKT cells were present in the intestine. NKT cells were rare in all sites of the small intestine, including an intraepithelial site. However, a considerable number of NKT cells were found at an intraepithelial site in the large intestine. This result was confirmed by both immunofluorescence and immunohistochemistry. In contrast to conventional NKT cells, NKT cells in the large intestine were CD8(+) or DN CD4(-)8(-). In the case of conventional NKT cells, their existence is known to depend on non-classical MHC class I-like antigens (i. e. CD1d) but not on classical MHC class I antigens. However, the NKT cells in the large intestine were independent of the presence of both CD1d and classical MHC class I antigens. These results were obtained using knockout mice lacking the corresponding genes and molecules. NKT cells in the large intestine were mainly alpha betaTCR(+) (> 75 %) but did not use an invariant chain of Valpha14Jalpha281, which is preferentially used by conventional NKT cells. These NKT cells did not bias the TCR-Vbeta usage toward Vbeta8. These findings suggest that the large intestine is a site in which unconventional NKT cells carrying the CD8(+) phenotype (or DN CD4(-)8(-)) are abundant and that these cells are independent of MHC and MHC-like antigens.